先進雷射石墨烯結構製程技術於生物分子元件應用之研究

Advanced Laser Processing Technology in Graphene for Applications of Biomolecule Devices

陳肇祈(Chen Zhao-Chi)

指導教授 ： 張天立

國立臺灣師範大學/科技與工程學院/機電工程學系/博士(2018年)

https://doi.org/10.6345/DIS.NTNU.DME.008.2018.E08

摘要

多功能生醫晶片的實現，用於人類的醫療保健上，除在生活中預防疾病發生外，更能即時甚至提前預測以獲得病患身體檢測之訊息，進一步於醫院接受更完整與深入治療，使病患在疾病之初期，立即獲得有效的診療。本研究在開發先進雷射(Advanced laser)於石墨烯(Graphene)圖案化電極製作及應用技術，以脈衝雷射剝離(Pulsed laser ablation, PLA)製程直寫(Direct writing)方式，在多層石墨烯(Multi-layer graphene, MLG)薄膜基材，進行製程材料的探討與感測元件的製作。本研究所使用的先進雷射系統，包括波長355 nm與532 nm的超快皮秒脈衝雷射(Ultrafast picosecond pulsed laser, 355/532-UPPL)及波長355 nm的奈秒脈衝雷射(Nanosecond pulsed laser, 355-NPL)。藉此先進雷射剝離製程，探討與多層石墨烯薄膜材料間之影響及特性分析，以製作感測電極結構元件。同時搭配微流體元件(Microfluidic device)設計和靜電紡絲(Electrospinning nanofibers)技術，實際應用於不同生物分子之元件檢測。

本研究以雷射製程技術於葡萄糖(Glucose)檢測元件的應用上，在加入葡萄糖氧化酶(Glucose oxidase, GOD)前/後，其皆呈現線性關係。然而，GOD的電特性是能夠直接通過監測多層石墨烯導電薄膜來獲得的，該電性響應顯示良好的葡萄糖檢測濃度範圍為1 mM到10 mM。此外，在微流體元件的應用上，以順時鐘(Clockwise)方式製作陣列柱狀微流道(Pillar array channels)結構，其具有少量的熔渣(Dross)與平滑的表面特徵，利用實驗結果之模型預測，玻璃基板(Glass substrate)的移除率(C)可達到0.04 μm/pulse。在靜電紡絲奈米線實驗中，PVA-G混合奈米線透過少量摻雜(濃度為6%)石墨烯薄片是可降低薄膜之電阻，並且能夠在溫度60 °C下進行操作，消耗電功率(Electric power, P)為265.25 mW。在相對溼度(Relative humidity, RH)為80%時，其較佳的濕度檢測之電性響應(Electric response)、反應時間(Response time)及恢復時間(Recovery time)性質分別顯示為66.4%、11 sec和35 sec。在聚合酶連鎖反應(Polymerase chain reaction, PCR)元件的實驗中，陣列孔洞之快速熱循環(Hole arrays-rapid thermal cycling, HA-RTC)元件顯示在60分鐘的時間能夠於人類多瘤性病毒(BKV)的標記物(Marker)，以及其在354鹼基對(Base pair, bp)的VP1片段完成診斷(增幅)，證實以多層石墨烯薄膜電極製作之微型加熱元件是較佳溫度保持以及熱傳導之特性。

本研究以先進脈衝雷射一次性製程(Single-step process)技術，達成免光罩(Mask-less)、微型化、快速製作及微量偵測之需求，在生醫檢測元件設計與應用，並以石墨烯材料製作薄膜檢測元件之特性，在靜電紡絲製作混合奈米線應用於生物分子之檢測獲得到驗證。

關鍵字

脈衝雷射剝離 ； 靜電紡絲奈米線 ； 微型加熱元件 ； 石墨烯 ； 葡萄糖 ； 微流體 ； 聚合酶連鎖反應元件

並列摘要

The realization of multi-functional biomedical sensors for human health care, not only to preventing diseases in life, but also predictive to obtain the patient's medical messages. These patients can receive effective medical treatment further at once after the disease and achieve faster healing compared to hospital diagnosis. In this study, the multi-layer graphene (MLG) thin-film based electrode structures were fabricated by pulsed laser ablation (PLA) direct writing for advanced laser processing technology. Among them, the wavelength of ultrafast picosecond pulsed laser (355/532-UPPL), and nanosecond pulsed laser (355-NPL) were used. Then the effects and and characterization of MLG thin films can be investigated. At the same time, the development of microfluidic device design and electrospun nanofibers technology can be applied to detect the different biomolecules.

Based on the laser processing technology to form the on-chip device for glucose detection, the linear I-V curves demostrated that the detection of GOD were obtained by monitoring the change of the electronic characteristics of the MLG thin-film based device. Here, the electrical respond revealed a good linear dependence in the glucose concentration range from 1 to 10 mM. For the application of microfluidic device, the reducing dross on the surface of ablated pillar array channels with the scanning curve process can be used at the optimal parameters in the clockwise direction. The C of glass device can reach the value of 0.04 μm/pulse that depends on the number of pulses applied to the microfluidic process by a simple model. For the application of electrospun nanowires, PVA-G hybrid nanofiber devices that operation was possible at temperatures of up to 60 °C with the minimal power consumption of 265.25 mW at the PVA-G concentration of 6%. When the Relative humidity (RH) was 80%, the humidity detection device indicated that the excellent sensing properties of the electric response, response time, and recovery time were 66.4%, 11 sec, and 35 sec, respectively. For the application of PCR, the HA-RTC PCR device was possibly shown BK virus (BKV) within 60 min where the marker and its VP1 fragment at 354 bp can be performed entirely diagnosis (amplification). The device with formed microheaters with the MLG thin-film electrodes was verified the good temperature retention and thermal conductivity.

Therefore, a single-step process can be integrated to achieve the requirements of mask-less, miniaturization, rapid production and small volume detection in the design and application of biomedical detection. Furthermore, the development potential of graphene based thin-film devices with electrospinning composite nanofibers was demonstrated the on-chip sensing device for biomolecule detection.

並列關鍵字

Pulsed laser ablation ； Electrospun nanofibers ； Microheaters ； Graphene ； Glucose ； Microfluidic ； PCR device

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